Project Summary and Abstract Specificity is a key characteristic of adult memory that emerges during early childhood. The neural mechanisms responsible for the ontogeny of memory specificity are unknown. Our lab and others have previously hypothesized that features of hippocampal development may regulate the transition from memory generalization to specificity during childhood. In line with this hypothesis, our lab has identified the development of the extracellular matrix ? and in particular, perineuronal nets ? as a potential regulator of memory specificity. This proposal will provide critical insight into the role of perineuronal nets in regulating the ontogeny of memory specificity. Aim 1 will use a cutting-edge optogenetic approach to elucidate how generalized versus specific memories are differentially represented in cellular memory engrams in the hippocampus. Aim 2 will use viral gene manipulation approach to reveal the critical requirement of perineuronal net protein HAPLN1 for memory specificity during adulthood. Aim 3 will use a complementary viral approach to examine whether HAPLN1 expression in the hippocampus of infants is sufficient to trigger to onset of memory specificity. This proposal will reveal for the first time a role for the extracellular matrix in regulating the development of memory functions, namely memory specificity. It will provide fundamental knowledge about the function of perineuronal nets in memory specificity, which may provide novel avenues for understanding and treating multiple brain disorders characterized by inappropriate memory generalization, such as generalized anxiety, depressive, and post-traumatic stress disorders.